Abstract
Objectives
In-vivo studies of the bioavailability of major components of the tumor necrosis factor alpha (TNFα) biosystem inside the gestational sac during embryogenesis have not been reported. We sought to determine the concentration of TNFα, soluble (s) TNFα receptors (sTNFR1, sTNFR2), and RANTES in the primate extraembryonic celomic fluid (ECF).
Methods
A validated timed-pregnant baboon animal model (N: 10) for experimental research in pregnancy was used to collect paired maternal blood and ECF samples in ongoing pregnancies. The concentrations (pg/dL) of TNFα, sTNFR1, sTNFR2, and RANTES were then determined by ELISA immunoassays.
Results
All animals delivered at term healthy newborns. The differential concentration of TNFα, sTNFR1, sTNFR2, and RANTES between the maternal plasma and the ECF could be determined with ratios for TNFα (5.4), sTNFR2 (1.85) and RANTES (3.59) that contrasted with that of sTNFR1 (0.07), which favored the gestational sac compartment. No significant correlations were noted between maternal plasma and ECF TNFR1, sTNFR2 and RANTES. There was a trend for a correlation between TNFα in maternal plasma and ECF (R=0.74; p=0.07).
Conclusions
We report the physiological concentrations of TNFα, sTNFR1, sTNFR2, and RANTES in extraembryonic celomic fluid during embryogenesis in primates.
Funding source: Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI
Funding source: The Laura Bush Women’s Health Research Institute at Texas Tech Health Science Center
Acknowledgments
The authors are grateful to Dr. Roberto Romero, Dr. Sam Edwin and staff at the Hutzel Women’s Hospital and the Perinatology Research Branch, NICHD/NIH/DHHS Laboratories for validating, performing and reporting the results of the Immunoassays. The authors also recognize Dr. Roman Wolf, at the Biological Resource Laboratory at the Oklahoma University, for his professional and technical help handling the animals and samples.
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Research funding: The study was supported by the Laura Bush Women’s Health Research Institute at Texas Tech Health Science Center and the Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. JLS, JCG and RB participated in the writing, interpretation of the data and in the final approval of the manuscript. JLS, DS performed literature reviews and prepared the manuscript cooperatively. JSF performed all the ultrasound-guided celocentesis, was responsible for the study design, drafted and critically revised the manuscript. All authors read and approved the final manuscript.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Not applicable.
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Ethical approval: The Oklahoma University Animal Care Committee approved the research protocol. The American Association for Accreditation of Laboratory Animal Care accredited the facilities at Oklahoma University.
References
1. Bazzoni, F, Beutler, B. The tumor necrosis factor ligand and receptor families. N Engl J Med 1996;334:1717–25. https://doi.org/10.1056/nejm199606273342607.Search in Google Scholar
2. Davis, JM, Narachi, MA, Alton, NK, Arakawa, T. Structure of human tumor necrosis factor alpha derived from recombinant DNA. Biochemistry 1987;26:1322–6. https://doi.org/10.1021/bi00379a018.Search in Google Scholar PubMed
3. Ruddle, NH. Tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta). Curr Opin Immunol 1992;4:327–32. https://doi.org/10.1016/0952-7915(92)90084-r.Search in Google Scholar PubMed
4. Vanden Berghe, W, Vermeulen, L, De Wilde, G, De Bosscher, K, Boone, E, Haegeman, G. Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol 2000;60:1185–95. https://doi.org/10.1016/s0006-2952(00)00412-3.Search in Google Scholar PubMed
5. Vilcek, J, Lee, TH. Tumor Necrosis Factor. New insights into the molecular mechanisms of its multiple actions. J Biol Chem 1991;266:7313. https://doi.org/10.1016/s0021-9258(20)89445-9.Search in Google Scholar
6. Aderka, D, Engelmann, H, Shemer-Avni, Y, Hornik, V, Galil, A, Sarov, B, et al.. Variation in serum levels of the soluble TNF receptors among healthy individuals. Lymphokine Cytokine Res 1992;11:157–9.Search in Google Scholar
7. Porteu, F, Nathan, C. Shedding of tumor necrosis factor receptors by activated human neutrophils. J Exp Med 1990;172:599–607. https://doi.org/10.1084/jem.172.2.599.Search in Google Scholar PubMed PubMed Central
8. Engelmann, H, Novick, D, Wallach, D. Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors. J Biol Chem 1990;265:1531–6. https://doi.org/10.1016/s0021-9258(19)40049-5.Search in Google Scholar
9. CCL5 C-C motif chemokine ligand 5 [Homo sapiens (human)] - gene - NCBI [Internet]. www.ncbi.nlm.nih.gov. Available from: https://www.ncbi.nlm.nih.gov/gene/6352.Search in Google Scholar
10. Donlon, TA, Krensky, AM, Wallace, MR, Collins, FS, Lovett, M, Clayberger, C, et al.. Localization of a human T-cell-specific gene, RANTES (D17S136E), to chromosome 17q11.2-q12. Genomics 1990;6:548–53. https://doi.org/10.1016/0888-7543(90)90485-d.Search in Google Scholar PubMed
11. Calleja-Agius, J, Muttukrishna, S, Jauniaux, E. The role of tumor necrosis factor-receptors in pregnancy with normal and adverse outcome. Int J Interferon Cytokine Mediat Res 2012;4:1–15. https://doi.org/10.2147/ijicmr.s22848.Search in Google Scholar
12. Gropper, MA. Evidence-based management of critically ill patients: analysis and implementation. Anesth Analg 2004;99:566–72. https://doi.org/10.1213/01.ane.0000123494.40145.b3.Search in Google Scholar PubMed
13. American college of chest physicians/society of critical care medicine consensus conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864–74.10.1097/00003246-199206000-00025Search in Google Scholar
14. Girardin, E, Roux-Lombard, P, Grau, GE, Suter, P, Gallati, H, Dayer, JM. Imbalance between tumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. The J5 Study Group. Immunol 1992;76:20–3.Search in Google Scholar
15. Samson, M, Libert, F, Doranz, BJ, Rucker, J, Liesnard, C, Farber, CM, et al.. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996;382:722–5. https://doi.org/10.1038/382722a0.Search in Google Scholar PubMed
16. Huiyun, Z, Haiwei, Y, Wenjing, M, Shaoheng, H. Induction of IL-13 production and upregulated expression of protease activated receptor-1 by RANTES in a mast cell line. Cytokine 2011;53:231–8. https://doi.org/10.1016/j.cyto.2010.10.005.Search in Google Scholar PubMed
17. Kroeze, KL, Jurgens, WJ, Doulabi, BZ, van Milligen, FJ, Scheper, RJ, Gibbs, S. Chemokine-mediated migration of skin-derived stem cells: predominant role for CCL5/RANTES. J Invest Dermatol 2009;129:1569–81. https://doi.org/10.1038/jid.2008.405.Search in Google Scholar PubMed
18. Honczarenko, M, Marcin, YL, Glodek, AM, Silberstein, LE, Silberstein, LE. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem cells 2006;24:1030–41. https://doi.org/10.1634/stemcells.2005-0319.Search in Google Scholar PubMed
19. Naworth, PP, Stern, DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986;163:740–5. https://doi.org/10.1084/jem.163.3.740.Search in Google Scholar PubMed PubMed Central
20. Boyle, JJ, Weissberg, PL, Bennett, MR. Tumor necrosis factor-alpha promotes macrophage-induced vascular smooth muscle cell apoptosis by direct and autocrine mechanisms. Arterioscler Thromb Vasc Biol 2003;23:1553–8. https://doi.org/10.1161/01.atv.0000086961.44581.b7.Search in Google Scholar PubMed
21. Soria, G, Ofri-Shahak, M, Haas, I, Yaal-Hahoshen, N, Leider-Trejo, L, Leibovich-Rivkin, T, et al.. Inflammatory mediators in breast cancer: coordinated expression of TNFα & IL-1β with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition. BMC Cancer 2011;12:1471–2407. https://doi.org/10.1186/1471-2407-11-130.Search in Google Scholar PubMed PubMed Central
22. Velasco-Velazquez, M, Jiao, X, De La Fuente, M, Pestell, TG, Ertel, A, Lisanti, M, et al.. CCR5 antagonist blocks metastasis of basal breast cancer cells. Cancer Res 2012;72:3839–50. https://doi.org/10.1158/0008-5472.can-11-3917.Search in Google Scholar
23. Gupta, M, Babic, A, Beck, AH, Terry, K. TNF-alpha expression, risk factors, and inflammatory exposures in ovarian cancer: evidence for an inflammatory pathway of ovarian carcinogenesis? Hum Pathol 2016;54:82–91. https://doi.org/10.1016/j.humpath.2016.03.006.Search in Google Scholar PubMed PubMed Central
24. WertelI, TR, Bednarek, W, Kotarski, J. Relationship between RANTES and dendritic cells in ovarian cancer patients. Front Biosci (Elite Ed). 2011:227–32. https://doi.org/10.2741/e237.Search in Google Scholar PubMed
25. Lu, W, Gersting, JA, Maheshwari, A, Christensen, RD, Calhoun, DA. Developmental expression of chemokine receptor genes in human fetus. Early Hum Dev 2005;81:489–96. https://doi.org/10.1016/j.earlhumdev.2004.10.022.Search in Google Scholar PubMed
26. Santolaya, J, Duval, J, Prespin, C, Vengalil, S, Bieniarz, A, Koures, A, et al.. Extracelomic fluid osmometry and electrolyte composition during early gestation in the baboon. Am J Obstet Gynecol 1998;179:1124–7.10.1016/S0002-9378(98)70117-6Search in Google Scholar PubMed
27. Santolaya-Forgas, J, De Leon-Luis, J, Espinoza, J, Goncalves, L, Romero, R. Solutes in maternal circulation and gestational sac compartments during early human development. Fetal Diagn Therap 2006;21:287–92, https://doi.org/10.1159/000091358.Search in Google Scholar PubMed
28. Santolaya-Forgas, J, Wolf, R, Edwin, S, Pitt, A, Nien, JK, Romero, R. VEGFR-1 and VEGFR-2 concentrations in extraembryonic celomic fluid: biological regulators of yolk sac vasculogenesis in primates. In: Proceedings of the 2006 Miami Nature Biotechnology Winter Symposium. http://www.med.miami.edu/mnbws/proceedings2006.html.2006.Search in Google Scholar
29. Santolaya-Forgas, J, De Leon-Luis, J, Shen, Z, McCorquodale, M. Chromosomal studies on 2mL of celomic fluid obtained during the fifth week of development in the timed-pregnant baboon model. J Reprod Med 2005;50:692–6.Search in Google Scholar
30. Santolaya-Forgas, J, De Leon-Luis, J, Galan, I. Can extra-embryonic celomic fluid be partially replaced with stem cell culture medium? Ultrasound Obstet Gynecol 2006;28:232–3. https://doi.org/10.1002/uog.2848.Search in Google Scholar PubMed
31. Santolaya-Forgas, J, Galan, I, De Leon-Luis, J, Wolf, R. A study to determine if human umbilical cord hematopoetic stem cells can survive in baboon extra-embryonic celomic fluid: a prerequisite for determining the feasibility of in-utero stem cell xeno-transplantation via celocentesis. Fetal Diagn Therap 2007;29:58–63.10.1159/000097112Search in Google Scholar PubMed
32. Santolaya-Forgas, J, DeLeon-Luis, J, Wilkins-Haug, L. Celocentesis for in utero stem cell therapy: where we now stand and future directions. Am J Perinatol 2007;24:277–81. https://doi.org/10.1055/s-2007-972925.Search in Google Scholar PubMed
33. Santolaya, JL, Galan, I, Di Stefano, VD, Jasani, S, De Leon-Luis, J, Wolf, R, et al.. Candidate biomarkers for acute rejection of pregnancy after in-utero cell-based therapy in pre-immune embryos via ultrasound-guided celocentesis. Am J Reprod Immunol 2012;68:181–4. https://doi.org/10.1111/j.1600-0897.2012.01150.x.Search in Google Scholar PubMed
34. Santolaya-Forgas, J, DeLeon-Luis, J, Friel, LA, Wolf, R. Application of the carnegie stages of development to unify human and baboon ultrasound findings early in pregnancy. Ultrasound Med Biol 2007;18:1400–5. https://doi.org/10.1016/j.ultrasmedbio.2007.03.005.Search in Google Scholar PubMed
35. Santolaya-Forgas, J, Edwin, S, Zeiter, K, Pitt, A, Pineles, B, Tarca, AL, et al.. The timed-pregnant baboon animal model can be used for determining the effect of differential bioavailability of soluble vascular endothelial growth factor. J Med Primatol 2007;36:370–4. https://doi.org/10.1111/j.1600-0684.2006.00205.x.Search in Google Scholar PubMed
36. Santolaya, JL, Kugler, L, Francois, L, Di Stefano, VD, Ebert, GA, Wolf, R, et al.. Baseline TNFa operational capacity in fetal and maternal circulation prior to the onset of labor: tuned for different purposes. Reprod Sci 2013;30:838–44. https://doi.org/10.1177/1933719112468953.Search in Google Scholar PubMed PubMed Central
37. Haider, S, Knöfler, M. Human tumour necrosis factor: physiological and pathological roles in placenta and endometrium. Placenta 2009;30:111–23.10.1016/j.placenta.2008.10.012Search in Google Scholar PubMed PubMed Central
38. Pavlov, OV, Niauri, DA, Selutin, AV, Selkov, SA. Coordinated expression of TNFalpha- and VEGF-mediated signaling components by placental macrophages in early and late pregnancy. Placenta 2016;42:28–36.10.1016/j.placenta.2016.04.008Search in Google Scholar PubMed
39. Chen, HL, Yang, YP, Hu, XL, Yelavarthi, KK, Fishback, JL, Hunt, JS. Tumor necrosis factor alpha mRNA and protein are present in human placental and uterine cells at early and late stages of gestation. Am J Pathol 1991;139:327–35.Search in Google Scholar
40. Yang, Y, Yelavarthi, KK, Chen, HL, Pace, JL, Terranova, PF, Hunt, JS., biochemical, and functional characteristics of tumor necrosis factor-alpha produced by human placental cytotrophoblastic cells. J Immunol 1993;150:5614–24.10.4049/jimmunol.150.12.5614Search in Google Scholar
41. King, A, Jokhi, PP, Smith, SK, Sharkey, AM, Loke, YW. Screening for cytokine mRNA in human villous and extravillous trophoblasts using the reverse-transcriptase polymerase chain reaction (RT-PCR). Cytokine 1995;7:364–71.10.1006/cyto.1995.0046Search in Google Scholar PubMed
42. Knofler, M, Mosl, B, Bauer, S, Griesinger, G, Husslein, P. TNF-alpha/TNFRI in primary and immortalized first trimester cytotrophoblasts. Placenta 2000;21:525–35.10.1053/plac.1999.0501Search in Google Scholar PubMed
43. Keogh, RJ, Harris, LK, Freeman, A, Baker, PN, Aplin, JDWhitley, GSet al.. Fetal-derived trophoblast use the apoptotic cytokine tumor necrosis factor-alpha-related apoptosis-inducing ligand to induce smooth muscle cell death. Circ Res 2007;100:834–41.10.1161/01.RES.0000261352.81736.37Search in Google Scholar PubMed
44. Lambin, S, van Bree, R, Vergote, I, Verhaeghe, J. Chronic tumor necrosis factor-α infusion in gravid C57Bl6/J mice accelerates adipose tissue development in female offspring. J Soc Gynecologic Investig 2006;13:558–65. https://doi.org/10.1016/j.jsgi.2006.09.001. Search in Google Scholar PubMed
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